Risk factors and healing factors for pharyngocutaneous fistula after total laryngectomy for laryngeal cancer: An epidemiological study.

To analyse the risk factors and healing factors of pharyngocutaneous fistula (PCF) in patients with laryngeal cancer after total laryngectomy, and to explore the relevant epidemiology. A retrospective analysis was conducted on laryngeal cancer patients who underwent total laryngectomy in our hospital from January 2010 to December 2022. The 349 patients included in the study were divided into a PCF group of 79 and a non-PCF group of 270. Perform one-way analysis of variance and multivariate logistic analysis on various data of patients included in the statistics, and analyse the risk factors and healing factors of PCF. Smoking, history of radiation therapy for laryngeal cancer, history of chemotherapy for laryngeal cancer, tumour location (larynx, pharynx, oesophagus), preoperative albumin, postoperative proteinaemia, <99 haemoglobin, postoperative haemoglobin, postoperative C-reactive protein (CRP) level are the risk factors for PCF. Also, radiation therapy and postoperative proteinaemia were the main reasons for preventing PCF healing. Smoking history, laryngeal cancer, radiation therapy, albumin, haemoglobin and CRP are risk factors for postoperative PCF after total laryngectomy, while radiation therapy and postoperative hypoalbuminaemia are key factors affecting PCF healing.

A review of nucleic acid-based detection methods for foodborne viruses: Sample pretreatment and detection techniques.

Viruses are major pathogens that cause food poisoning when ingested via contaminated food and water. Therefore, the development of foodborne virus detection technologies that can be applied throughout the food distribution chain is essential for food safety. A common nucleic acid-based detection method is polymerase chain reaction (PCR), which has become the gold standard for monitoring food contamination by viruses due to its high sensitivity, and availability of commercial kits. However, PCR-based methods are labor intensive and time consuming, and are vulnerable to inhibitors that may be present in food samples. In addition, the methods are restricted with regard to site of analysis due to the requirement of expensive and large equipment for sophisticated temperature regulation and signal analysis procedures. To overcome these limitations, optical and electrical readout biosensors based on nucleic acid isothermal amplification technology and nanomaterials have emerged as alternatives for nucleic acid-based detection of foodborne viruses. Biosensors are promising portable detection tools owing to their easy integration into compact platforms and ability to be operated on-site. However, the complexity of food components necessitates the inclusion of tedious preprocessing steps, and the lack of stability studies on residual food components further restricts the practical application of biosensors as a universal detection method. Here, we summarize the latest advances in nucleic acid-based strategies for the detection of foodborne viruses, including PCR-based and isothermal amplification-based methods, gene amplification-free methods, as well as food pretreatment methods. The principles, strengths/disadvantages, and performance of each method, problems to be solved, and future prospects for the development of a universal detection method are discussed.

Recent Advances in Biosensor Development for the Detection of Viral Particles in Foods: A Comprehensive Review.

Viral foodborne diseases cause serious harm to human health and the economy. Rapid, accurate, and convenient approaches for detecting foodborne viruses are crucial for preventing diseases. Biosensors integrating electrochemical and optical properties of nanomaterials have emerged as effective tools for the detection of viruses in foods. However, they still face several challenges, including substantial sample preparation and relatively poor sensitivity due to complex food matrices, which limit their field applications. Hence, the purpose of this review is to provide an overview of recent advances in biosensing techniques, including electrochemical, SERS-based, and colorimetric biosensors, for detecting viral particles in food samples, with emerging techniques for extraction/concentration of virus particles from food samples. Moreover, the principle, design, and advantages/disadvantages of each biosensing method are comprehensively described. This review covers the recent development of rapid and sensitive biosensors that can be used as new standards for monitoring food safety and food quality in the food industry.

Memory effect of spider major ampullate silk in loading-unloading cycles and the structural connotations.

Spider silk is repeatedly stretched while performing biological functions. There is a close relationship between the shape change of the fibre materials and their mechanical properties. However, the effect of the deformation and interval time on the structure and tensile behaviour properties of spider silk after repeatedly stretching by given strain value has been rarely reported. Here we found that major ampullate silk (MAS) can revert its tensile behaviour independent of its previous loading history via intervals of approximately 8 s to 5 min with constant and increased elongation, respectively, after being subjected to yield and hardening regions. The true stress-true strain curve beyond a given value of true strain is independent from the previous loading history of the sample. Even after longer intervals (≥1 h), MAS can reproduce the last tensile behaviour via one stretched. Despite recognizing the development of irreversible deformations in the material when tested in air, the reversible change in tensile behaviour outside the spider silk's elastic region has rarely been observed before. MAS has at least one proper ground state that allows it to present good shape and mechanical behaviour memory in terms of longitudinal stretching, functioning as a new strategy to achieve certain tensile properties. The analysis of the true stress-true strain curves was performed from a series of loading‒unloading tests to evaluate the evolution of those mechanical parameters with the cycle number. The elastic modulus measured in the loading steps increases monotonously with increasing values of true strain reached in the cycles. In contrast, a marginal variation is found in the values of the yield stress measured in the different cycles. The memory and variation in the mechanical behaviour and performance of MAS can be accounted for through the irreversible and reversible deformation micromechanisms and its combination in which the viscoelasticity of the material plays a leading role. These findings may be helpful to guide the biomimetic design of novel fibre materials such as spider silk gut via artificially stretching spider silk glands.

Paper-Based Radial Flow Assay Integrated to Portable Isothermal Amplification Chip Platform for Colorimetric Detection of Target DNA.

A novel integrated detection system that introduces a paper-chip-based molecular detection strategy into a polydimethylsiloxane (PDMS) microchip and temperature control system was developed for on-site colorimetric detection of DNA. For the paper chip-based detection strategy, a padlock probe DNA (PLP)-mediated rolling circle amplification (RCA) reaction for signal amplification and a radial flow assay according to the Au-probe labeling strategy for visualization were optimized and applied for DNA detection. In the PDMS chip, the reactions for ligation of target-dependent PLP, RCA, and labeling were performed one-step under isothermal temperature in a single chamber, and one drop of the final reaction solution was loaded onto the paper chip to form a radial colorimetric signal. To create an optimal analysis environment, not only the optimization of molecular reactions for DNA detection but also the chamber shape of the PDMS chip and temperature control system were successfully verified. Our results indicate that a detection limit of 14.7 nM of DNA was achieved, and non-specific DNAs with a single-base mismatch at the target DNA were selectively discriminated. This integrated detection system can be applied not only for single nucleotide polymorphism identification, but also for pathogen gene detection. The adoption of inexpensive paper and PDMS chips allows the fabrication of cost-effective detection systems. Moreover, it is very suitable for operation in various resource-limited locations by adopting a highly portable and user-friendly detection method that minimizes the use of large and expensive equipment. Supplementary Information: The online version contains supplementary material available at 10.1007/s13206-023-00101-7.

Photothermally Active Core-Shell Catalyst Based on UiO-66 and Polydopamine for Highly Effective Detoxification of Nerve Agents.

A new, photothermally active, catalytic composite (Fe3O4@PD@UiO-66) based on UiO-66 and polydopamine (PD) was prepared for the decomposition of chemical warfare agents (CWAs). An iron oxide nanoparticle was introduced to enable rapid recovery after the reaction. The PD layer enabled conversion of the absorbed light into heat under infrared (IR) irradiation and increased the reaction temperature, thereby increasing the reaction rate. Dendrimer-functionalized silica particles (NH2-DS) were used as heterogeneous catalyst regenerators instead of N-ethylmorpholine. Under IR irradiation, a mixture of Fe3O4@PD@UiO-66 and NH2-DS was effective as a heterogeneous catalyst for degrading DMNP, with a 5 min half-life in water. Without IR irradiation, the half-life of DMNP was 45 min using the same catalyst mixture. Various bases including arginine, histidine, and D4 were directly modified on the surface of Fe3O4@PD@UiO-66 and used without NH2-DS or N-ethylmorpholine in order to compare their reactivities. Furthermore, a mixture of Fe3O4@PD@UiO-66 and NH2-DS was used for the decomposition of nerve agents, including sarin (GB), soman (GD), and VX, under IR-LED irradiation. Remarkably, GB was effectively decomposed with a half-life of 4.2 min, and GD demonstrated a half-life of 8.7 min. VX was hydrolyzed with a half-life of 14.0 min.

Vitamin D Activates miR-126a-5p to Target GSK-3ß and Alleviates Systemic Lupus Erythematosus in MRL/LPR Mice.

BACKGROUND: The etiology of systemic lupus erythematosus (SLE) is complex, and the disease is thus difficult to cure. In this regard, it has been established that SLE patients are characterized by differing levels of vitamin D-hydroxylation; however, the direct effects of vitamin D (VitD) in these patients remain unknown. OBJECTIVE: Therefore, we investigated the effects and mechanisms of action of VitD in the context of SLE. METHODS: The effects of VitD on MRL/LPR mice were studied by synthesizing glycogen synthase kinase-3ß (GSK-3ß)-interfering lentiviruses and transfecting with miR-126a-5p mimics. Changes in the body weight of mice were recorded for 6 weeks. Western blotting was performed to determine the levels of T-bet, GATA3, and GSK-3ß protein expression, and qRT-PCR was performed to determine the levels of miR-126a-5p and GSK-3ß mRNA expression. ELISA was performed to determine the levels of ANA, dsDNA, and snRNP/Sm in mice serum. RESULTS: GSK-3ß and miR-126a-5p were expressed at high and low levels, respectively, in MRL/LPR mice. VitD (30 ng/kg) was found to reduce the expression of GSK-3ß and increase miR-126a-5p expression, which targets GSK-3ß. T-bet and GATA3 were found to be positively regulated by miR-126a-5p and VitD and negatively regulated by GSK-3ß. The body weight of mice was not altered by VitD. ANA, dsDNA, and snRNP/Sm were positively regulated by miR- 126a-5p and VitD and negatively regulated by GSK-3ß. The effects of GSK-3ß were enhanced in response to the inhibition of miR-126a-5p expression. CONCLUSION: VitD upregulated miR-126a-5p to target GSK-3ß expression, thereby alleviating the SLE in MRL/LPR mice.

A rare case of a mother with gestational diabetes complicated with fulminant type 1 diabetes mellitus post-delivery.

Fulminant type 1 diabetes mellitus (FT1DM) is recognised as a novel subtype of type 1 diabetes mellitus characterised by the abrupt onset of insulin-deficient hyperglycaemia and ketoacidosis. Fulminant type 1 diabetes mellitus is known to be associated with pregnancy and had been associated with high fetal mortality. We report a case of a gestational diabetes mellitus (GDM) mother complicated with FT1DM immediately post-delivery. A 29-year-old Malay lady who was diagnosed with GDM at 19 weeks of pregnancy, underwent emergency lower segment caesarean section (EMLSCS) due to fetal distress at 36 weeks of gestation; 18 h post-EMLSCS, she developed abrupt onset Diabetic ketoacidosis (DKA) (blood glucose 33.5 mmol/L, pH 6.99, bicarbonate 3.6 mmol/L, ketone 4.4 mmol/L and HbA1c 6.1%). She received standard DKA treatment and discharged well. Her plasma C-peptide level 3 weeks later showed that she has no insulin reserve (C-peptide <33 pmol/L, fasting blood glucose (FBS) 28 mmol/L). Her pancreatic autoantibodies were negative. This case highlights that FT1DM not only can occur in pregnancy with normal glucose tolerance but can also complicate mother with GDM.

Prediction of Facial Emotion Recognition Ability in Patients With First-Episode Schizophrenia Using Amplitude of Low-Frequency Fluctuation-Based Support Vector Regression Model.

Objective: There were few studies that had attempted to predict facial emotion recognition (FER) ability at the individual level in schizophrenia patients. In this study, we developed a model for the prediction of FER ability in Chinese Han patients with the first-episode schizophrenia (FSZ). Materials and Methods: A total of 28 patients with FSZ and 33 healthy controls (HCs) were recruited. All subjects underwent resting-state fMRI (rs-fMRI). The amplitude of low-frequency fluctuation (ALFF) method was selected to analyze voxel-level spontaneous neuronal activity. The visual search experiments were selected to evaluate the FER, while the support vector regression (SVR) model was selected to develop a model based on individual rs-fMRI brain scan. Results: Group difference in FER ability showed statistical significance (P < 0.05). In FSZ patients, increased mALFF value were observed in the limbic lobe and frontal lobe, while decreased mALFF value were observed in the frontal lobe, parietal lobe, and occipital lobe (P < 0.05, AlphaSim correction). SVR analysis showed that abnormal spontaneous activity in multiple brain regions, especially in the right posterior cingulate, right precuneus, and left calcarine could effectively predict fearful FER accuracy (r = 0.64, P = 0.011) in patients. Conclusion: Our study provides an evidence that abnormal spontaneous activity in specific brain regions may serve as a predictive biomarker for fearful FER ability in schizophrenia.

Airway Microbiota in Patients With Synchronous Multiple Primary Lung Cancer: The Bacterial Topography of the Respiratory Tract.

Microbes and microbiota dysbiosis are correlated with the development of lung cancer; however, the airway taxa characteristics and bacterial topography in synchronous multiple primary lung cancer (sMPLC) are not fully understood. The present study aimed to investigate the microbiota taxa distribution and characteristics in the airways of patients with sMPLC and clarify specimen acquisition modalities in these patients. Using the precise positioning of electromagnetic navigation bronchoscopy (ENB), we analyzed the characteristics of the respiratory microbiome, which were collected from different sites and using different sampling methods. Microbiome predictor variables were bacterial DNA burden and bacterial community composition based on 16sRNA. Eight non-smoking patients with sMPLC in the same pulmonary lobe were included in this study. Compared with other sampling methods, bacterial burden and diversity were higher in surface areas sampled by bronchoalveolar lavage (BAL). Bacterial topography data revealed that the segment with sMPLC lesions provided evidence of specific colonizing bacteria in segments with lesions. After taxonomic annotation, we identified 4863 phylotypes belonging to 185 genera and 10 different phyla. The four most abundant specific bacterial community members detected in the airway containing sMPLC lesions were Clostridium, Actinobacteria, Fusobacterium, and Rothia, which all peaked at the segments with sMPLC lesions. This study begins to define the bacterial topography of the respiratory tract in patients with sMPLC and provides an approach to specimen acquisition for sMPLC, namely BAL fluid obtained from segments where lesions are located.

Porcine Endogenous Retroviruses: Quantification of the Viral Copy Number for the Four Miniature Pig Breeds in China.

Domestic pigs has served not only as one of the most important economy livestock but also as ideal organ-source animals owing to similarity in anatomy, physiology, and organ size to humans. Howerer, the barrier of the cross-species transmission risk of porcine endogenous retrovirus (PERVs) blocked the pig-to-human xenotransplantation. PERVs are integrated into pigs' genomes and cannot be eliminated by designated or specified pathogen-free breeding. PERVs are an important biosafety issue in xenotransplantation because they can be released from normal pig cells and infect human cells in vitro under certain conditions. Screening and analyzing the presence of PERVs in pig genome will provide essential parameters for pig breed sources. In China, four miniature pig breeds, such as Guizhou miniature pig (GZ), Bama miniature pig (BM), Wuzhishan miniature pig (WZS), and Juema miniature pig (JM), were the main experimental miniature pig breeds, which were widely used. In this study, PCR was performed to amplify env-A, env-B, and env-C for all individuals from the four breeds. The results revealed that PERV env-A and env-B were detected in all individuals and the lowest ratios of PERV env-C was 17.6% (3/17) in the GZ breed. Then, PERV pol and GAPDH were detected using the droplet digital PCR (ddPCR) method. As the reference of GAPDH copy number, the copy numbers of PERVs were at the median of 12, 16, 14, and 16 in the four miniature pig breeds (GZ, BM, WZS, and JM), respectively. Furthermore, the copy number of the PERV pol gene in many organs from the GZ breed was analyzed using ddPCR. The copy numbers of PERV pol gene were at the median of 7 copies, 8 copies, 8 copies, 11 copies, 5 copies, 6 copies, and 7 copies in heart, liver, spleen, lung, kidney, muscle, and skin, and the maximum number was 11 copies in the lung. The minimum number was 5 copies in the kidney as the reference of GAPDH. These data suggest that GZ breed has the lower PERVs copy number in the genome, and may be an ideal organ-source miniature pig breed for the study of the pig-to-human xenotransplantation.

Rolling Circle Amplification-based Copper Nanoparticle Synthesis on Cyclic Olefin Copolymer Substrate and Its Application in Aptasensor.

This study aimed to develop a label-free fluorescent aptasensor for the detection of diazinon (DZN) on a cyclic olefin copolymer (COC) substrate. The aptasensor design was based on rolling circle amplification (RCA) technology and the use of self-assembled copper nanoparticles (CuNPs). A dual-function (DF) probe, capable of binding to circular DNA and an aptamer, was designed and immobilized on a COC-bottom 96-well plate. An aptamer was used for selective recognition of DZN, and the specific site of the aptamer that strongly reacted with DZN was successfully identified using circular dichroism (CD) analysis. In presence of DZN, the aptamer and DZN formed a strong complex, thus providing an opportunity for hybridization of the DF probe and circular DNA, thereby initiating an RCA reaction. Repetitive poly thymine (T) sequence with a length of 30-mer, generated in the RCA reaction, served as a template for the synthesis of fluorescent copper nanoparticles, emitting an orange fluorescence signal (at approximately 620 nm) proportional to the amount of RCA product, within 10 min under UV irradiation. The CuNP fluorescence was imaged and quantified using an image analysis software. A linear correlation of the fluorescence signal was confirmed in the DZN concentration range of 0.1-3 ppm, with a detection limit of 0.15 ppm. Adoption of a label-free detection method, utilizing RCA and fluorescent CuNPs on COC substrates, reduced the need for complex equipment and requirements for DZN analysis, thereby representing a simple and rapid sensing method circumventing the limitations of current complex and labor-intensive methods. Electronic Supplementary Material ESM: The online version of this article (doi:10.1007/s12257-021-0220-0) contains supplementary material, which is available to authorized users.

Sequential sagittal alignment changes in the cervical spine after occipitocervical fusion.

BACKGROUND: There are few studies regarding sequential changes in the sagittal alignment of the upper and lower cervical regions of the spine after occipitocervical fusion (OCF). In addition, no comparisons of cervical sagittal alignment (CSA) between patients with craniocervical junction disorders (CJDs) and normal populations have been reported. AIM: To compare the CSA of patients with CJDs with that of normal controls and investigate the sequential changes in the CSA of the upper and lower cervical spine after OCF. METHODS: Eighty-four patients who underwent OCF (OCF group) and 42 asymptomatic volunteers (control group) were included. Radiographic parameters, including the occipital to C2 angle (O-C2a), occipital and external acoustic meatus to axis angle (O-EAa), C2-7 angle (C2-7a), and pharyngeal inlet angle (PIA), were measured and compared pre- and postoperatively. The correlations among the parameters were analyzed using Pearson's correlation test. RESULTS: The O-C2a and PIA of the OCF group were smaller than those of the control group, while their O-EAa and C2-7a values were larger than those of the normal controls. There were no significant differences in O-C2a, C2-7a, or PIA in the OCF group at baseline, 1 mo, or the final follow-up after surgery. The Pearson's correlation results showed that there were significant correlations between the O-C2a and C2Ta, C2-7a, C2-7 sagittal vertical axis (SVA), and PIA at 1 mo after OCF surgery and between O-C2a and O-EAa, C2Ta, C2-7a, C2-7 SVA, and PIA at the final follow-up. CONCLUSION: Patients with CJDs have a more kyphotic upper CSA and a more lordotic lower CSA than normal controls. The effectiveness of OCF surgery in restoring CSA may be limited by the realignment of the craniocervical junction being neglected. The reduction in O-C2a after OCF surgery may increase C2-7a and decrease PIA.

Silencing of circ_OSBPL10 affects the functional behaviors of oral squamous cell carcinoma cells by the miR-299-3p/CDK6 axis.

BACKGROUND: Circular RNAs (circRNAs) are increasingly implicated in the development of oral squamous cell carcinoma (OSCC). Here, we explored the precise role of circRNA oxysterol binding protein like 10 (circ_OSBPL10, circ_0008549) in OSCC pathogenesis. METHODS: Ribonuclease (RNase) R assay was performed to assess the stability of circ_OSBPL10. The levels of circ_OSBPL10, microRNA (miR)-299-3p and cyclin-dependent kinase 6 (CDK6) mRNA were gauged by qRT-PCR. CDK6 protein level was measured by western blot. Cell proliferation was detected by MTT and colony formation assays. Cell cycle distribution and apoptosis were measured by flow cytometry. Cell migration and invasion were evaluated using transwell assay. Dual-luciferase reporter assay was used to identify the relationship between miR-299-3p and circ_OSBPL10 or CDK6. Animal studies were performed to evaluate the role of circ_OSBPL10 in tumor growth in vivo. RESULTS: Circ_OSBPL10 was up-regulated in OSCC tissues and cells. Silencing of circ_OSBPL10 hindered cell proliferation, cell cycle progression, colony formation, migration, invasion, and promoted apoptosis in vitro and diminished tumor growth in vivo. Mechanistically, circ_OSBPL10 directly targeted miR-299-3p, and circ_OSBPL10 silencing affected cell functional properties in vitro by up-regulating miR-299-3p. CDK6 was a direct and functional target of miR-299-3p. The circ_OSBPL10/miR-299-3p axis regulated cell functional properties in vitro via CDK6. Moreover, circ_OSBPL10 acted as a competing endogenous RNA (ceRNA) to regulate CDK6 expression through miR-299-3p. CONCLUSION: Our present findings first demonstrate that circ_OSBPL10 can regulate the functional behaviors of OSCC cells at least partially by miR-299-3p/CDK6 axis, highlighting circ_OSBPL10 as a promising therapeutic target for OSCC.

Long non-coding RNA CCAT2 drives the growth of laryngeal squamous cell carcinoma via regulating YAP activity.

Emerging evidence suggests that long non-coding RNA (lncRNA) is closely associated with numerous human diseases, including cancer. However, the functional relevance of lncRNA in human laryngeal squamous cell carcinoma (LSCC) is largely unknown. In the current study, we described CCAT2, a previously unappreciated oncogenic lncRNA in LSCC. CCAT2 was significantly upregulated in human LSCC tissue and serum samples, associated with larger tumor volume, higher clinical stage, and poorer differentiation status. Lentivirus-mediated CCAT2 knockdown notably repressed the cell viability, colony formation, and DNA synthesis rate of LSCC. Screening of transcription factors revealed that YAP/TEAD activity was affected by CCAT2 in LSCC cells. Further, CCAT2 directly binds to YAP protein and blocks the phosphorylation of YAP induced by LATS1, resulting in the nuclear translocation of YAP and the activation of YAP oncogenic targets, such as CTGF, CYR61 and AMOTL2. Importantly, we also confirmed the regulation of CCAT2 on YAP activity in vivo based on nude mice model. Altogether, we identified a novel lncRNA that controls YAP nucleocytoplasmic shuttling and promotes LSCC cell proliferation. Given the importance of YAP in tumorigenesis and progression, our results provide insights to intervene LSCC by targeting the CCAT2/YAP axis.

Trends in sensor development toward next-generation point-of-care testing for mercury.

Mercury is one of the most common heavy metals and a major environmental pollutant that affects ecosystems. Since mercury and its compounds are toxic to humans, even at low concentrations, it is very important to monitor mercury contamination in water and foods. Although conventional mercury detection methods, including inductively coupled plasma mass spectrometry, atomic absorption spectroscopy, and gas chromatography-mass spectrometry, exhibit excellent sensitivity and accuracy, they require operation by an expert in a sophisticated and fully controlled laboratory environment. To overcome these limitations and realize point-of-care testing, many novel methods for direct sample analysis in the field have recently been developed by improving the speed and simplicity of detection. Commonly, these unconventional sensors rely on colorimetric, fluorescence, or electrochemical mechanisms to transduce signals from mercury. In the case of colorimetric and fluorescent sensors, benchtop methods have gradually evolved through technology convergence to give standalone platforms, such as paper-based assays and lab-on-a-chip systems, and portable measurement devices, such as smartphones. Electrochemical sensors that use screen-printed electrodes with carbon or metal nanomaterials or hybrid materials to improve sensitivity and stability also provide promising detection platforms. This review summarizes the current state of sensor platforms for the on-field detection of mercury with a focus on key features and recent developments. Furthermore, trends for next-generation mercury sensors are suggested based on a paradigm shift to the active integration of cutting-edge technologies, such as drones, systems based on artificial intelligence, machine learning, and three-dimensional printing, and high-quality smartphones.

Oral glutamine inhibits tumor growth of gastric cancer bearing mice by improving immune function and activating apoptosis pathway.

Gastric cancer is one of the most common cancers in the world. It has been shown that exogenous glutamine (GLN) can inhibit the growth of tumor in vivo, but the relationship between GLN and gastric cancer has not been studied. The gastric cancer bearing mouse model was constructed and taken GLN orally at the same time, and the results found that oral GLN (1 or 2 g/kg/d) significantly inhibited the growth rate of tumor and reduce the weight of tumor tissues. Immunohistochemistry showed that oral GLN significantly reduced the PCNA index, which further proved that GLN could inhibit the growth of tumor cells. At the same time, TUNEL assay showed that oral GLN significantly enhanced the apoptosis levels of tumor cells. In addition, GLN reduced GSH levels in tumor tissues, but increased the levels of GSH in plasma, improved the T-lymphocyte transformation rate and NK cell activity, significantly inhibited the secretion of TNF-α and promoted the secretion of IL-2, thus regulating the immune function in vivo. Further detection of apoptosis pathway showed that oral GLN significantly enhanced the expression of pro-apoptotic factor Bad and inhibited the expression of Bcl-2. Meanwhile, GLN significantly increased the activities of Caspase-3, Caspase-8, caspase-9 and PARP. GSH activator NAC had a similar effect to GLN, which could improve the immune function and activate apoptosis pathway, while GSH inhibitor BSO significantly blocked the regulation of GLN, destroyed the immune balance and inhibited apoptosis, but IL-2 significantly blocked the anti-apoptotic effect of BSO. Therefore, oral GLN can improve immune function and activate apoptosis pathway through GSH, and then inhibit the growth of tumor in vivo.

Hyperandrogenism caused by ovarian Leydig cell tumour: finding the needle in a haystack.

Leydig cell tumours (LCTs) of the ovary are rare ovarian tumours that usually present with hyperandrogenism. Conventional radiological imagings are helpful in localising these tumours. However, some tumours may be too small to be localised before curative surgical removal. It is important to identify these androgen-secreting neoplasms which originate mostly from adrenals or ovaries because they are potentially malignant and require specific treatment. When conventional imagings are unrevealing, selective ovarian and adrenal venous sampling (SOAVS) is the next option. We report a case of LCT that was localised by SOAVS after results from other imaging modalities remained inconclusive.

Tumor mutation burden associated with miRNA-gene interaction outcome mediates the survival of patients with liver hepatocellular carcinoma.

Tumor mutation burden (TMB) is associated with immunogenic responses and the survival of cancer patients. This study demonstrates how TMB levels impact the immune-related cells, genes, and miRNAs, and how miRNA/gene interactions respond to variations in the survival rate of patients with liver hepatocellular carcinoma (LIHC). LIHC patients were divided into two groups, either a low TMB (< median) or a high TMB (≥ median) group. We found that high TMB plays a positive role in immune-mediated infiltration, generating more CD4 T-cells and memory B cells. Among the 21 immune genes that altered significantly, only C9orf24 and CYP1A1 were expected to up-regulate in LIHC patients with high TMB. A total of 19 miRNAs, which regulate various functional pathways, were significantly altered in patients with LIHC. One of the miRNA/gene pair, hsa-miR-33a/ALDH1A3 was significantly associated with the survival rate of LIHC patients. Our results suggest that LIHC patients with high TMB can be treated more effectively with immunotherapy.